Antibacterial efficacy of antimicrobial peptide-functionalized hydrogel particles combined with vancomycin and oxacillin antibiotics.

The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA's minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.

Lyotropic liquid crystal elastomers for drug delivery.

Silicone elastomers like polydimethylsiloxane (PDMS) possess a combination of attractive material and biological properties motivating their widespread use in biomedical applications. Development of elastomers with capacity to deliver active therapeutic substances in the form of drugs is of particular interest to produce medical devices with added functionality. In this work, silicone-based lyotropic liquid crystal elastomers with drug-eluting functionality were developed using PDMS and triblock copolymer (diacrylated Pluronic F127, DA-F127). Various ternary PDMS-DA-F127-H2O compositions were explored and evaluated. Three compositions were found to have specific properties of interest and were further investigated for their nanostructure, mechanical properties, water retention capacity, and morphology. The ability of the elastomers to encapsulate and release polar and nonpolar substances was demonstrated using vancomycin and ibuprofen as model drugs. It was shown that the materials could deliver both types of drugs with a sustained release profile for up to 6 and 5 days for vancomycin and ibuprofen, respectively. This works demonstrates a lyotropic liquid crystal, silicone-based elastomer with tailorable mechanical properties, water retention capacity and ability to host and release polar and nonpolar active substances.

Multifunctional Surface Modification of PDMS for Antibacterial Contact Killing and Drug-Delivery of Polar, Nonpolar, and Amphiphilic Drugs.

Medical device-associated infections pose major clinical challenges that emphasize the need for improved anti-infective biomaterials. Polydimethylsiloxane (PDMS), a frequently used elastomeric biomaterial in medical devices, is inherently prone to bacterial attachment and associated infection formation. Here, PDMS surface modification strategy is presented consisting of a cross-linked lyotropic liquid crystal hydrogel microparticle coating with antibacterial functionality. The microparticle coating composed of cross-linked triblock copolymers (diacrylated Pluronic F127) was deposited on PDMS by physical immobilization via interpenetrating polymer network formation. The formed coating served as a substrate for covalent immobilization of a potent antimicrobial peptide (AMP), RRPRPRPRPWWWW-NH2, yielding high contact-killing antibacterial effect against Staphylococcus epidermidis and Staphylococcus aureus. Additionally, the coating was assessed for its ability to selectively host polar, amphiphilic, and nonpolar drugs, resulting in sustained release profiles. The results of this study put forward a versatile PDMS modification strategy for both contact-killing antibacterial surface properties and drug-delivery capabilities, offering a solution for medical device-associated infection prevention.